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131.
Role of UEV-1, an Inactive Variant of the E2 UbiquitinConjugating Enzymes, in In Vitro Differentiation and Cell Cycle Behavior of HT-29-M6 Intestinal Mucosecretory Cells 总被引:1,自引:0,他引:1 下载免费PDF全文
132.
Jezabel Varadé José Ramón Lamas Miguel Fernández-Arquero Juan Ángel Jover Emilio G. de la Concha Alfonso Martínez Benjamín Fernández-Gutierrez Elena Urcelay 《Nitric oxide》2009,20(3-4):171-174
Nitric oxide has been described as a trigger for the synthesis of proinflammatory mediators and as a cytotoxic molecule with a pivotal role in apoptosis at the joints of rheumatoid arthritis (RA) patients. Polymorphisms in the NOS2A gene, which codes for the inducible nitric oxide synthase [(i)NOS], have been tested for association with several autoimmune diseases such as Crohn’s disease or type 1 diabetes. Moreover, the existence of correlated levels of (i)NOS protein and synovial cell apoptosis in RA patients, pointed to NOS2A as a good candidate gene involved in RA predisposition. The role of NOS2A was studied in 405 Spanish RA patients and in 398 ethnically matched healthy controls, through the analysis of five SNPs: two at the NOS2A promoter (rs2779251 and 2779248), other two exonic markers (Asp346Asp (rs1137933) and Ser608Leu (rs22518)) and the last one located at intron 7 (rs3729508). We also included other two widely-used promoter polymorphisms: the insertion/deletion (TAAA/-) and the (CCTTT)n microsatellite. No individual association of each single-marker or haplotype was found with RA susceptibility. Our data show the low linkage disequilibrium between these NOS2A SNPs and the alleles of the (CCTTT)n microsatellite, corroborating in a Spanish population the observation previously described in British and Gambian population. The present data do not support a causative role of NOS2A polymorphisms in RA predisposition. 相似文献
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134.
Ferreres F Figueiredo R Bettencourt S Carqueijeiro I Oliveira J Gil-Izquierdo A Pereira DM Valentão P Andrade PB Duarte P Barceló AR Sottomayor M 《Journal of experimental botany》2011,62(8):2841-2854
Class III peroxidases (Prxs) are plant enzymes capable of using H(2)O(2) to oxidize a range of plant secondary metabolites, notably phenolic compounds. These enzymes are localized in the cell wall or in the vacuole, which is a target for secondary metabolite accumulation, but very little is known about the function of vacuolar Prxs. Here, the physiological role of the main leaf vacuolar Prx of the medicinal plant Catharanthus roseus, CrPrx1, was further investigated namely by studying its capacity to oxidize co-localized phenolic substrates at the expense of H(2)O(2). LC-PAD-MS analysis of the phenols from isolated leaf vacuoles detected the presence of three caffeoylquinic acids and four flavonoids in this organelle. These phenols or similar compounds were shown to be good CrPrx1 substrates, and the CrPrx1-mediated oxidation of 5-O-caffeoylquinic acid was shown to form a co-operative regenerating cycle with ascorbic acid. Interestingly, more than 90% of total leaf Prx activity was localized in the vacuoles, associated to discrete spots of the tonoplast. Prx activity inside the vacuoles was estimated to be 1809 nkat ml(-1), which, together with the determined concentrations for the putative vacuolar phenolic substrates, indicate a very high H(2)O(2) scavenging capacity, up to 9 mM s(-1). Accordingly, high light conditions, known to increase H(2)O(2) production, induced both phenols and Prx levels. Therefore, it is proposed that the vacuolar couple Prx/secondary metabolites represent an important sink/buffer of H(2)O(2) in green plant cells. 相似文献
135.
Züchner S Dallman J Wen R Beecham G Naj A Farooq A Kohli MA Whitehead PL Hulme W Konidari I Edwards YJ Cai G Peter I Seo D Buxbaum JD Haines JL Blanton S Young J Alfonso E Vance JM Lam BL Peričak-Vance MA 《American journal of human genetics》2011,(2):581-206
Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions. 相似文献
136.
Di Pierro M Lu R Uzzau S Wang W Margaretten K Pazzani C Maimone F Fasano A 《The Journal of biological chemistry》2001,276(22):19160-19165
Zonula occludens toxin (Zot) is an enterotoxin elaborated by Vibrio cholerae that increases intestinal permeability by interacting with a mammalian cell receptor with subsequent activation of intracellular signaling leading to the disassembly of the intercellular tight junctions. Zot localizes in the bacterial outer membrane of V. cholerae with subsequent cleavage and secretion of a carboxyl-terminal fragment in the host intestinal milieu. To identify the Zot domain(s) directly involved in the protein permeating effect, several zot gene deletion mutants were constructed and tested for their biological activity in the Ussing chamber assay and their ability to bind to the target receptor on intestinal epithelial cell cultures. The Zot biologically active domain was localized toward the carboxyl terminus of the protein and coincided with the predicted cleavage product generated by V. cholerae. This domain shared a putative receptor-binding motif with zonulin, the Zot mammalian analogue involved in tight junction modulation. Amino acid comparison between the Zot active fragment and zonulin, combined with site-directed mutagenesis experiments, confirmed the presence of an octapeptide receptor-binding domain toward the amino terminus of the processed Zot. 相似文献
137.
Ramirez Apan AA Pérez-Castorena AL de Vivar AR 《Zeitschrift für Naturforschung. C, Journal of biosciences》2004,59(3-4):237-243
A new phytochemical study of Mortonia greggii (Celastraceae) afforded four friedelan derivatives (1-4), three lupanes (5-7), retusine (8), two esterified polyhydroxyagarofurans (9-10), mortonin C (11) and photomortonin C (12). The anti-inflammatory activity on carrageenan and 12-O-tetradecanoylphorbol-13-acetate induced models of inflammation, as well as the ability to inhibit the nitric oxide (NO) produced by lipopolysaccharide-stimulated mouse peritoneal macrophages were evaluated for the main metabolites. Our results showed that the friedelan dehydrocanophyllic acid methyl ester (1) exhibits an anti-inflammatory effect which could be related to an inhibition of prostaglandin and NO production. The activity of lupeol (5), 29-hydroxylupeol (6) and 29-hydroxylupenone (7) might be involved with the prostanoid synthesis. The presence of the hydroxy groups in 6 appears to be important for activity. The edema inhibition capacity of retusine (8) could be related to a reduction of the prostaglandin production. The agarofuran derivative 10 is an NO inhibitor whose activity is probably not involved in the synthesis of prostaglandins. 相似文献
138.
139.
Mauro?Fasano Alessio?Bocedi Marco?Mattu Massimo?Coletta Paolo?AscenziEmail author 《Journal of biological inorganic chemistry》2004,9(7):800-806
Hemopexin (HPX) serves as a trap for toxic plasma heme, ensuring its complete clearance by transportation to the liver. Moreover, HPX-heme has been postulated to play a key role in the homeostasis of nitric oxide (NO). Here, the thermodynamics for NO binding to rabbit ferrous HPX-heme as well as the EPR and optical absorption spectroscopic properties of rabbit ferrous nitrosylated HPX-heme (HPX-heme-NO) are reported. The value of the dissociation equilibrium constant for NO binding to rabbit ferrous HPX-heme (i.e., H) is (1.4±0.2)×10–7 M, at pH 7.0 and 10.0 °C; the value of H is unaffected by sodium chloride. At pH 7.0, rabbit ferrous HPX-heme-NO is a six-coordinate heme-iron species, characterized by an X-band EPR spectrum with an axial geometry and by =146 mM–1 cm–1 at 419 nm. At pH 4.0, rabbit ferrous HPX-heme-NO is a five-coordinate heme-iron species, characterized by an X-band EPR spectrum with three-line splitting centered at 334 mT and by =74 mM–1 cm–1 at 387 nm. The pKa value of the reversible pH-induced six- to five-coordinate spectroscopic transition is 4.8±0.1 in the absence of sodium chloride and 4.3±0.1 in the presence of 1.5×10–1 M sodium chloride. This result is in agreement with the effect of sodium chloride on rabbit HPX-heme stability. The present data have been analyzed in parallel with those of a related heme model compound and heme-protein systems. 相似文献
140.
Downloading the information stored in relational databases into XML and other flat formats is a common task in bioinformatics. This periodical dumping of information requires considerable CPU time, disk and memory resources. YAdumper has been developed as a purpose-specific tool to deal with the integral structured information download of relational databases. YAdumper is a Java application that organizes database extraction following an XML template based on an external Document Type Declaration. Compared with other non-native alternatives, YAdumper substantially reduces memory requirements and considerably improves writing performance. 相似文献